title: The effect of methotrexate on corneal neovascularization in rabbits.
abstract: OBJECTIVE
  To determine the efficacy of topical application and subconjunctival injection of methotrexate in the treatment of corneal neovascularization using a rabbit model.
  
  
  METHODS
  Corneal neovascularization was induced with suturing in 12 rabbits (24 eyes). One week after suturing, 12 rabbits were divided into 3 groups of 4 rabbits each. One group was treated with topical methotrexate 2 mg/mL, a second group with topical methotrexate 4 mg/mL, both 4 times a day, and the third group with a subconjunctival injection of methotrexate 2 mg/mL (0.1 mL). Control rabbits received a balanced salt solution instead of methotrexate. The area of corneal neovascularization was measured using light microscopy, 1 week and 2 weeks after initiation of the treatment. The concentrations of vascular endothelial growth factor and interleukin-6 in corneal tissue were measured 2 weeks after initiation of the treatment.
  
  
  RESULTS
  The area of neovascularization was significantly reduced in the treatment groups compared with the control group (P < 0.05). No significant difference was found in the area of neovascularization between the groups treated with the 2 doses of topical methotrexate. The concentrations of vascular endothelial growth factor and interleukin-6 were significantly lower in the treatment groups compared with the control group (P < 0.05), but no difference was observed among the treatment groups. The corneal epithelium, stroma, and endothelium showed a normal appearance.
  
  
  CONCLUSIONS
  Topical and subconjunctival methotrexate application may be useful for treating corneal neovascularization, but further study regarding dosage, route of administration, and indications for methotrexate should be performed in the future.
authors.affiliation: Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, The College of Medicine, The Catholic University, Seoul, Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Byun
authors.forename: Sung Kun
authors.initials: SK
authors.lastname: Chung
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D003315:Cornea / Q000378:metabolism; D016510:Corneal Neovascularization / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000378:metabolism; D008727:Methotrexate / Q000008:administration & dosage*; D011817:Rabbits; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; D015850:Interleukin-6; D042461:Vascular Endothelial Growth Factor A; D008727:Methotrexate